Doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) is one of the most effective chemotherapeutic agents used in the management of pediatric neoplastic disorders during the past 20 years. However, its use has been limited by well-characterized, dose-related cardiac toxicity. Recently, cardiac dysfunction has been noted in pediatric patients who had received doxorubicin years before. This article summarizes current information regarding the pathophysiology and risk factors associated with cardiotoxicity and reviews detection methods and treatments of this condition.
Get full access to this article
View all access options for this article.
References
1.
Lipshultz S. , Colan S., Gelber R., et al: Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood . N Engl J Med324:808-815, 1991
2.
Steinherz L. , Steinherz P., Tan C., et al: Cardiac toxicity 4 to 20 years after completing anthracycline therapy. JAMA266:1672-1677, 1991
3.
Saltiel E., McGuire W.: Doxorubicin (Adriamycin) cardiomyopathy. Western J Med139:332-340, 1983
4.
Halliwell B. , Bomford A.: ICRF-187 and doxorubicin-induced cardiac toxicity. N Engl J Med320:399-400, 1989
5.
Dorr R.: Chemoprotectants for cancer chemotherapy. Semin Oncol18:48-58, 1991
6.
Inchiosa M., Smith C.: Effects of ibuprofen on doxorubicin toxicity. Res Commun Chem Pathol Pharmacol67:63-78, 1990
7.
Doroshow J.: Doxorubicin-induced cardiac toxicity. N Engl J Med324:843-845, 1991
8.
Steinherz L. , Steinherz P.: Delayed anthracycline cardiac toxicity. Cancer Principles Practice Oncol5:1-15, 1991
9.
Unverferth D. , Magorien R., Leier C., et al: Doxorubicin cardiotoxicity. Cancer Treat Rev2:149-164, 1982
10.
Borow K., Henderson C., Neuman A.: Assessment of left ventricular contractility in patients receiving doxorubicin . Ann Intern Med99:750-756, 1983
11.
Steinherz L. , Steinherz P.: Delayed cardiac toxicity from anthracycline therapy. Pediatrician18:49-52, 1991
12.
Guyton A.: Textbook of Medical Physiology (ed 6). Philadelphia, PA, Saunders, 1981 , pp 150-175; 274-287
13.
Bristow M., Mason J., Billingham M., et al: Dose-effect and structure function relationship in doxorubicin cardiomyopathy. Am Heart J102:709-718, 1981
14.
Goorin A., Borow K., Goldman A., et al: Congestive heart failure due to adriamycin cardiotoxicity—Its natural history in children. Cancer47:2810-2816, 1981
15.
Steinherz L. , Graham T., Hurwitz R., et al: Guidelines for cardiac monitoring of children during and after anthracycline therapy: Report of the cardiology committee of the Children's Cancer Study Group. Pediatrics89:942-949, 1992
16.
Lipshultz S. : Personal communication, Fall 1989
17.
Sallon S.: Unpublished manuscript, 1989
18.
Larsen R.: Electrocardiographic changes and arrhythmias after cancer therapy in children and young adults. Am J Cardiol70:1991 (abstr)
19.
Gazes P.: Clinical Cardiology: A Bedside Approach. Chicago, IL, Year Book Medical, 1983
20.
Walts R.: Severe and fatal anthracycline cardiotoxicity at cumulative doses below 400 mg/m2: Evidence for enhanced toxicity with multi-agent chemotherapy . Am J Hematol36:217-218, 1991 (abstr)
21.
Larsen R., Jakacki R., Vetter V., et al: Electrocardiographic changes and arrhythmias after cancer therapy in children and young adults. Am J Cardiol70:73-77, 1992
22.
Goorin A., Chauvenet A., Perez-Atayde A., et al: Initial congestive heart failure 6-10 years after doxorubicin chemotherapy for childhood cancer. J Pediatr116:144-147, 1990
23.
Klewer S., Goldberg S., Donnerstein R., et al: Dobutamine stress echocardiography: A sensitive indicator of diminished myocardial function in asymptomatic doxorubicin-treated long-term survivors of childhood cancer. J Am Coll Cardiol19:394-401, 1992 (abstr)
24.
Weesner K., Bledsoe M., Chauvenet A., et al: Exercise echocardiography in the detection of anthracycline cardiotoxicity. Cancer68:435-438, 1991
25.
Yeung S., Yoong C., Spink J., et al: Functional myocardial impairment in children treated with anthracyclines for cancer. Lancet337:816-817, 1991
26.
Lipshultz S. , Colan S., Sallow S., et al: Afterload reduction therapy in long-term survivors of childhood cancer treated with doxorubicin. Am Heart Assoc: 64th Scientific Session, 1991 (abstr)
27.
Santostasi G., Kutty R., Krishna G., et al: Increased toxicity of anthracycline antibiotics induced by calcium entry blockers in cultured cardiomyocytes. Toxicol AppPharmacol108:140-149, 1991
28.
Arico M., Pedroni E., Nespoli L., et al: Long-term survival after heart transplantation for doxorubicin-induced cardiomyopathy. Arch Dis Child66:985-986, 1991
29.
Hitchcock-Bryan, Gelber R, Cassady R., et al: The impact of induction anthracycline on long-term failure-free survival in childhood acute lymphoblastic leukemia . Med Pediatr Oncol14:211-215, 1986
30.
Carter M., Thompson E., Simone J.: The survivors of childhood solid tumors. Pediatr Clin North Am38:505-526, 1991
31.
Meyer R.: Echocardiography, in Adams F, Emmanouilides G (eds): Moss' Heart Disease in Infants, Children, and Adolescents. Baltimore, MD, Williams and Wilkins, 1983, pp 58-82
32.
Yamada T., Matsumari A., Tamaki N., et al: Detection of adriamycin cardiotoxicity with indium-111 labeled Actinomyosin monoclonal antibody imaging. Jpn Circ J55:377-383, 1991 (abstr)
33.
Merz B., Hager T.: Diffusing adverse effects of anticancer drugs. JAMA250:459, 1983
34.
Rajagapalon E. , Politi P, Sinha, et al: Adriamycin-induced free radical formation in the perfused rat heart: Implications for cardiotoxicity . Cancer Res48:4766-4769, 1988
35.
Speyer J., Green M., Kramer E., et al: Protective effect of the bispiperazinedione ICRF-187 against doxorubicin-induced cardiac toxicity in women with advanced breast cancer . N Engl J Med319:745-752, 1988
36.
Powis G.: Metabolism and reactions of quinoid anticancer agents. Pharmacol Ther35:57-62, 1987
37.
Green M., Speyer J., et al: A prospective randomized trial of ICRF-187 for prevention of cumulation doxorubicin-induced cardiac toxicity in women with breast cancer . Cancer Treat Rev17:161-163, 1990
38.
Meadows A., Krejmas N., Belasis J.: The Medical Cost of Cure: Sequelae in Survivors of Childhood Cancer . New York, NY, Raven, p 263, 1980
